Environmental Engineering Reference
In-Depth Information
hormone, epidermal growth factor (EGF), or
ʱ
2
-glycoprotein or addition of a
pH-sensitive moiety according to the biological characteristics of the tumor
tissue.
As with other delivery systems, the drug delivery potential of polymeric
micelles may still be further enhanced by attaching targeting ligands to the
micelle surface. The attachment of various specific ligands to the water-
exposed termini of hydrophilic blocks could be used to improve the targeting
of micelles and micelle-incorporated drugs. Among those ligands one can
name various sugar moieties [
49
], transferrin [
46
] and folate residues [
50
]
since many target cells, especially cancer cells, overexpress appropriate
receptors (such as transferrin and folate receptors) on their surface. Thus, it
was shown that galactose- and lactose-modified micelles made of
PEGpolylactide copolymer specifically interact with lectins, thus modeling
targeting delivery of the micelles to hepatic sites [
51
]. Transferrin-modified
micelles based on PEG and poly (ethyleneimine) sized between 70 and 100 nm
are expected to target tumors with overexpressed transferring receptors [
46
].
Active targeting makes use of characteristics shown by the tumor cells, such
as overexpression of cell surface tumor-associated antigens that are at low
levels in normal tissue cells, as well as of the tumor-specific antigens and
relatively more acidic nature of tumor (pH 7.0) than normal tissue (pH 7.4).
Specific interactions between the targeting components with antigens
displayed on target tissues cause the selective accumulation of drug in the
target tissue. Active targeting decreases adverse side effects, because the drug
accumulates only in the tumor sites and it allows the drugs cellular uptake
through endocytosis [
52
]. Micelles with surface-attached specific antibodies,
also called immunomicelles, provide an opportunity for targeting in term of
diversity of targets and specificity of interactions. Micelle attached antibodies
retain their ability to specifically interact with their antigens.
Micelles equipped with folate ligands are used mainly for the intracellular
transport of the drug. After intracellular transport of folate-equipped micelles,
the drug carried by micelles should also be released intracellularly; this
problem is solved by the pH sensitivity of PMs that enables selective drug
release in the intracellular acidic compartment of endosomes with pH 5-6.
Such micelles are crucial to the carriers for delivery of materials that should
become pharmaceutically effective after entering the cell. Folate behaves as a
ligand having high affinity for its receptors, folate-binding proteins that are
selectively overexpressed on the surface of the cancer cells [
53
,
54
]. Elevated
levels of folate receptors are expressed on epithelial tumors of various organs
such as colon, lung, prostate, ovaries, mammary glands, and brain [
55
]. Thus,
the folate conjugates with an appropriate design can be directed to the tumor
cells in the body and internalized in the target cells via receptor-mediated
endocytosis.
Transferrin also acts as a suitable ligand for targeting tumor tissue, because
the receptors for transferrin are overexpressed on cancer cells in correlation
with the degree of malignancy [
56
]. Transferrin is an 80-kDa glycoprotein
